The determination of the blood-sugar level without direct contact with the blood, in particular without a special withdrawal of blood for this purpose, has been the subject of intensive medical research and development for more than two decades. The main objective thereby is the provision of a compact portable measuring apparatus for diabetics, which ideally can quickly provide reliable sugar values at the most through skin contact and without injuring the skin. Despite considerable efforts by numerous researchers, which have produced a large number of interesting approaches to a solution, to date no satisfactory measuring apparatus of this type has reached market readiness.
The prior art, which at this point can be cited only in extracts, deals both with in vivo as well as in vitro measurement, where very often a transfer is made directly from experimental in vitro results to the in vivo case. However, a transfer of this kind is in principle untenable, since it does not take into consideration at all or only incompletely the considerable complications of the interactions of all blood constituents and the solid tissue with light.
Thus, for example, in reality the proposal sometimes made of the analysis of the NIR light scattered back from the living body is a problem per se in a class of its own, in which the informative value of the scattered light is firstly questionable. Since scattered photons follow a nonlinear path, influenced by multiple scattering, back to the surface of the body, it must be decided at the detector which portion of light has run through a blood vessel at all and thus has information about the blood-sugar level. Such a source localization by itself is technically complex and is described, e.g. in DE 103 11 408 [U.S. Pat. No. 7,251,518].
Some sources therefore dedicate themselves primarily to the question of the physical measured variable that is to be used for glucose metering. The metrological details that an in vivo measurement would actually require are, in contrast, simply assumed to be technically soluble.
Thus, for example, U.S. Pat. No. 5,009,230 proposes measuring the change of the polarization of linearly polarized IR light when passing through perfused tissue, in concrete terms the rotation of the polarization plane by glucose molecules. The measurable light intensity behind a polarization filter is used to determine the concentration. It is thereby considered important for the sensitivity to change periodically between polarization directions perpendicular to one another.
It is known from U.S. Pat. No. 5,222,496 that the intensity of transmitted or reflected NIR light is to be placed in proportion to one another for several wavelengths in order to measure the glucose level. In particular light around 1600 nm wavelength is used, which is absorbed particularly well by glucose due to molecular fluctuations. In contrast, for this wavelength range water has a local absorption minimum. In order to compensate for the signals of other blood constituents, as well as the influence of the is surrounding tissue or, for example, the pigmentation of the skin with the in vivo measurement, U.S. Pat. No. 5,222,496 suggests the additional use of at least one further wavelength in the vicinity of the first, which in turn is not to be absorbed by glucose. Particular importance is attached to the slight difference of the wavelengths—less than 300 nm, preferably 60 nm—in order to ensure the same type of scatter behavior.
However, both sources are not concerned at all, for example, with the movement of the blood in the living organism. Also the knowledge of the temperature of the blood, doubtlessly necessary for spectrometric analysis, is referred to only briefly in U.S. Pat. No. 5,009,230, but by no means dealt with.
It is presumably due to the obviously immense complexity of the measurement task that indirect methods for determining blood sugar are also repeatedly proposed. Photoacoustic measurement is cited by way of example here, in which living tissue is irradiated with different wavelengths in order to detect the thermal expansion during the absorption of the radiation in the form of detectable ultrasonic waves on the skin's surface, see, e.g. U.S. Pat. No. 6,484,044. The wavelengths are also selected hereby according to the known absorption maximums of glucose, and likewise differential measurements are carried out for the purpose of signal isolation.
However, the fundamental problem of complexity is thus by no means circumvented, let alone solved. As already with the backscatter of photons, here too the information content of the sound signals is uncertain, their precise source localization is unclear and their formation certainly influenced by numerous highly individual and possibly even changeable tissue parameters. The photoacoustic method is ultimately a highly empirical method, which evidently has difficulty finding a standard calibration for broad applicability.
In conclusion, the GlucoWatch® method should be referenced as prior art, which is the only one on the market so far with FDA approval. GlucoWatch® indeed does not require a blood sample for analysis, but is attached to the skin of the wearer such that it can take up fluid through the skin. Users have frequently reported skin irritations and, furthermore, even the manufacturer advises against using GlucoWatch® as the only means of judging the correct insulin dosage.
The applicant believes a method for noninvasive blood glucose measurement will generally not be able to do without empirical data interpretation. However, this should remain limited in the interest of the most universal possible applicability of a system of this type to partial areas of the method that can be monitored well.
The following objects must be attained in order to create a noninvasive system:                1. Blood-sugar metering in flowing, pulsing blood (in vitro) recording empirical, largely universal calibration curves,        2. Transferring the method from the in vitro structure to preferably large blood vessels (e.g. aorta) by                    a. Source localization, elimination of signals is without information,            b. Compensation for tissue and skin influences on the remaining signal,            c. In situ temperature determination in the blood vessel and interstitial tissue for application of the calibration curves.                        
Considerable preliminary work has already been published by the applicant re points 2a and 2b in DE 103 11 408. The object 2c is the subject matter of future work and will be submitted in a separate application in due course. The present application deals solely with object 1. U.S. Pat. No. 5,222,496 is deemed to be the closest pertinent prior art in this case.
The in vitro determination of the blood-glucose level is of interest per se for integration into dialysis equipment.
Studies in the US show the importance of the continuous monitoring above all in the case of dialysis patients with diabetes. In the absence of suitable apparatuses, cases of death have already been recorded.